Metabolic Activation of the Toxic Natural Products From Herbal and Dietary Supplements Leading to Toxicities

Frontiers in Pharmacology

Lin Guo¹  Shuang Xia¹  Yi-Kun Wang²  Yan Miao²  Bi-Kui Zhang²  Wen Qun Li² 

[1] Department of Pharmacy, The Second Xiangya Hospital, Central South University, Changsha, China;Institute of Clinical Pharmacy, Central South University, Changsha, China;

关键词: herbal and dietary supplements-induced liver injury;    natural products;    metabolic activation;    reactive metabolites;    toxicity;   

DOI  :  10.3389/fphar.2021.758468

来源: DOAJ

【 摘 要 】

Currently, herbal and dietary supplements have been widely applied to prevent and treat various diseases. However, the potential toxicities and adverse reactions of herbal and dietary supplements have been increasingly reported, and have gradually attracted widespread attention from clinical pharmacists and physicians. Metabolic activation of specific natural products from herbal and dietary supplements is mediated by hepatic cytochrome P450 or intestinal bacteria, and generates chemical reactive/toxic metabolites that bind to cellular reduced glutathione or macromolecules, and form reactive metabolites-glutathione/protein/DNA adducts, and these protein/DNA adducts can result in toxicities. The present review focuses on the relation between metabolic activation and toxicities of natural products, and provides updated, comprehensive and critical comment on the toxic mechanisms of reactive metabolites. The key inductive role of metabolic activation in toxicity is highlighted, and frequently toxic functional groups of toxic natural products were summarized. The biotransformation of drug cytochrome P450 or intestinal bacteria involved in metabolic activation were clarified, the reactive metabolites-protein adducts were selected as biomarkers for predicting toxicity. And finally, further perspectives between metabolic activation and toxicities of natural products from herbal and dietary supplements are discussed, to provide a reference for the reasonable and safe usage of herbal and dietary supplements.

【 授权许可】

Unknown